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T Cells in Tumors and Blood Predict Outcome in Follicular Lymphoma Treated with Rituximab

Wahlin, Bjorn Engelbrekt; Sundstrom, Christer; Holte, Harald; Hagberg, Hans; Erlanson, Martin; Nilsson-Ehle, Herman; Lindén, Ola LU ; Nordstrom, Marie; Ostenstad, Bjorn and Geisler, Christian H., et al. (2011) In Clinical Cancer Research 17(12). p.4136-4144
Abstract
Purpose: T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown. Experimental Design: Using flow cytometry, we evaluated the T cells in tumors and/or blood in a total of 250 follicular lymphoma patients included in two Nordic Lymphoma Group randomized trials that compared single rituximab with IFN-alpha 2a-rituximab combinations. Results: In univariate analysis, higher levels of CD3(+), CD4(+), and CD8(+) T cells in both tumors and blood correlated with superior treatment responses, and in multivariate analysis, tumor-CD3(+) (P = 0.011) and blood-CD4(+) (P = 0.029) cells were independent. CD4(+) cells were... (More)
Purpose: T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown. Experimental Design: Using flow cytometry, we evaluated the T cells in tumors and/or blood in a total of 250 follicular lymphoma patients included in two Nordic Lymphoma Group randomized trials that compared single rituximab with IFN-alpha 2a-rituximab combinations. Results: In univariate analysis, higher levels of CD3(+), CD4(+), and CD8(+) T cells in both tumors and blood correlated with superior treatment responses, and in multivariate analysis, tumor-CD3(+) (P = 0.011) and blood-CD4(+) (P = 0.029) cells were independent. CD4(+) cells were favorable regardless of treatment arm, but CD8(+) cells were favorable only in patients treated with single rituximab, because IFN-alpha 2a improved responses especially in patients with low CD8(+) cell levels. Higher levels of blood-CD3(+) (P = 0.003) and blood-CD4(+) (P = 0.046) cells predicted longer overall survival, and higher levels of blood-CD8(+) cells longer times to next treatment (P = 0.046). Conclusions: We conclude that therapeutic effects of rituximab are augmented by tumor-associated T cells for rapid responses and by systemic T cells for sustained responses. CD4(+) and CD8(+) cells are both favorable in patients treated with rituximab. IFN-alpha 2a abrogates the negative impact of few CD8(+) cells. Clin Cancer Res; 17(12); 4136-44. (C) 2011 AACR. (Less)
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Clinical Cancer Research
volume
17
issue
12
pages
4136 - 4144
publisher
American Association for Cancer Research
external identifiers
  • wos:000291644700030
  • scopus:79959237067
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-11-0264
language
English
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yes
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6bde5780-22f2-4f9d-9f62-c0e943eb7d77 (old id 2056730)
date added to LUP
2011-08-02 09:00:50
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2017-09-17 03:39:56
@article{6bde5780-22f2-4f9d-9f62-c0e943eb7d77,
  abstract     = {Purpose: T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown. Experimental Design: Using flow cytometry, we evaluated the T cells in tumors and/or blood in a total of 250 follicular lymphoma patients included in two Nordic Lymphoma Group randomized trials that compared single rituximab with IFN-alpha 2a-rituximab combinations. Results: In univariate analysis, higher levels of CD3(+), CD4(+), and CD8(+) T cells in both tumors and blood correlated with superior treatment responses, and in multivariate analysis, tumor-CD3(+) (P = 0.011) and blood-CD4(+) (P = 0.029) cells were independent. CD4(+) cells were favorable regardless of treatment arm, but CD8(+) cells were favorable only in patients treated with single rituximab, because IFN-alpha 2a improved responses especially in patients with low CD8(+) cell levels. Higher levels of blood-CD3(+) (P = 0.003) and blood-CD4(+) (P = 0.046) cells predicted longer overall survival, and higher levels of blood-CD8(+) cells longer times to next treatment (P = 0.046). Conclusions: We conclude that therapeutic effects of rituximab are augmented by tumor-associated T cells for rapid responses and by systemic T cells for sustained responses. CD4(+) and CD8(+) cells are both favorable in patients treated with rituximab. IFN-alpha 2a abrogates the negative impact of few CD8(+) cells. Clin Cancer Res; 17(12); 4136-44. (C) 2011 AACR.},
  author       = {Wahlin, Bjorn Engelbrekt and Sundstrom, Christer and Holte, Harald and Hagberg, Hans and Erlanson, Martin and Nilsson-Ehle, Herman and Lindén, Ola and Nordstrom, Marie and Ostenstad, Bjorn and Geisler, Christian H. and Brown, Peter de Nully and Lehtinen, Tuula and Maisenholder, Martin and Tierens, Anne M. and Sander, Birgitta and Christensson, Birger and Kimby, Eva},
  issn         = {1078-0432},
  language     = {eng},
  number       = {12},
  pages        = {4136--4144},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {T Cells in Tumors and Blood Predict Outcome in Follicular Lymphoma Treated with Rituximab},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-11-0264},
  volume       = {17},
  year         = {2011},
}